title: Early antipsychotic response to aripiprazole in adolescents with schizophrenia: predictive value for clinical outcomes.
abstract: OBJECTIVE
  In adults with chronic schizophrenia, most symptom decreases occur in the first few weeks of antipsychotic treatment, and nonresponse at week 2 predicts a later nonresponse. The trajectory of antipsychotic response and the predictive value of early antipsychotic effects were investigated for ultimate outcome in adolescent schizophrenia, where such data are still lacking.
  
  
  METHODS
  This post hoc analysis of a 6-week, randomized, double-blinded trial of aripiprazole (n = 196) versus placebo (n = 98) evaluated if adolescents 13 to 17 years old with schizophrenia exhibited substantial symptomatic improvement to aripiprazole in the first few treatment weeks and whether early response (ER) versus early nonresponse (ENR) predicted clinically relevant outcomes. ER decreased at least 20% and ENR decreased less than 20% in Positive and Negative Syndrome Scale (PANSS) total score at week 2 (ER2/ENR2) or 3 (ER3/ENR3). Ultimate response decreased at least 40% in PANSS score.
  
  
  RESULTS
  Nearly 50% of the PANSS decrease was achieved by week 2 and up to 75% by week 3. ER2/ER3 subjects showed significantly greater improvement than ENR subjects in PANSS total score, PANSS positive and negative subscale scores, and functionally relevant outcomes. In general, ER3 had better sensitivity, specificity, and positive and negative predictive values than ER2 for predicting ultimate response. ER2 subjects were 8.8 times (95% confidence interval 4.0-19.4) and ER3 subjects were 8.6 times (95% confidence interval 4.5-16.6) more likely to achieve remission at week 6 (p < .0001) than ENR2 and ENR3 subjects, respectively, although adverse events were similar.
  
  
  CONCLUSIONS
  Like adults with chronic schizophrenia, adolescents with early-phase schizophrenia exhibited most symptomatic improvement early during aripiprazole treatment, with week 3 improvements having the best predictive power. Although requiring extension, these results may inform clinical decision making. Clinical trial registration information-Aripiprazole in Adolescents with Schizophrenia, http://clinicaltrials.gov/, NCT00102063.
authors.affiliation: Zucker Hillside Hospital, Hofstra North Shore Long Island Jewish School of Medicine, Glen Oaks, NY 11004, USA. ccorrell@lij.edu
authors.forename: Christoph U
authors.initials: CU
authors.lastname: Correll
authors.forename: Joan
authors.initials: J
authors.lastname: Zhao
authors.forename: William
authors.initials: W
authors.lastname: Carson
authors.forename: Ron
authors.initials: R
authors.lastname: Marcus
authors.forename: Robert
authors.initials: R
authors.lastname: McQuade
authors.forename: Robert A
authors.initials: RA
authors.lastname: Forbes
authors.forename: Raymond
authors.initials: R
authors.lastname: Mankoski
mesh_terms: D000293:Adolescent; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000068180:Aripiprazole; D004311:Double-Blind Method; D006801:Humans; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D010919:Placebos; D011237:Predictive Value of Tests; D011569:Psychiatric Status Rating Scales; D015363:Quinolones / Q000008:administration & dosage / Q000494:pharmacology*; D012559:Schizophrenia / Q000188:drug therapy*; D012680:Sensitivity and Specificity; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D010879:Piperazines; D010919:Placebos; D015363:Quinolones; D000068180:Aripiprazole